Processing and Analyzing Mass Spectrometry Proteomics Data for the Longevity Consortium

Translational Genomics Research Inst, Phoenix AZ

Investigators

Linked publications & trials

Abstract

Overall Summary The processes contributing to human aging, age-related diseases (e.g., Alzheimer’s disease and related dementias; ADRD), and longevity are notoriously complex and multifactorial. This complexity makes it difficult to identify longevity-promoting (i.e. geroprotective) interventions and targets, clinically useful biomarkers, and predictive models that could enhance human health. One strategy to overcome this is to assess the findings of one study in the light of findings from studies with different designs or foci – i.e., integrate or ‘triangulate’ those findings – such as cell models, cross species studies and human association studies. Such integration could lead to further validation of individual findings and put into context any one or group of such findings. The LC will embark on an unprecedented level of integration by capitalizing on its legacy findings and 20+ year history, network of investigators, expanded data sharing capabilities, unique resources, and assay capabilities, and pursue 5 projects (P1-P5) taking different approaches. Each is designed to address a specific overarching objective of the RFA and contribute data and results for use in integrated analyses. In addition, an Integrated Analysis Core (IAC) and an Administrative Core (AC) will be developed to address further objectives in the RFA. The five projects are rooted in research efforts and discoveries in the last LC funding cycle: P1 will study diverse human populations to determine the contexts within which longevity-related factors exhibit associations; P2 will study genomically-mediated evolutionary processes contributing to longevity; P3 will study extreme longevity (EL) and its relationship to ADRD in diverse human populations; P4 will study aging rate indicators in response to candidate geroprotective drugs in mice; and P5 will explore novel cell systems and constructs derived from individuals with EL and other longevity related phenotypes. The IAC will seek to integrate results and data across these projects by developing appropriate infrastructure and analytical methods, as well as engaging in analyses with the research teams pursuing each project. The AC will oversee and track progress of the research as well as monitor financial and related activities. The LC will also work with the NIA-funded Data Management and Coordinating Center (DMCC) and its Exceptional Longevity Translational Resources (ELITE) internet data portal to enable broader access to LC data. Working groups will enhance specific activities, e.g., data sharing and training, and, importantly, a Pharmaceutical and Translational Advisory Panel (PTAP) will be established to enable discussions about the best way to follow up findings in drug development contexts. The LC will identify compelling and verified insights into human longevity based on the proposed studies and its expansive integrated approach and ultimately identify novel vetted candidate pre-clinical drug targets, geroprotective interventions, health biomarkers, and predictive models of longevity-related phenotypes.